Computational modeling of orthodromically evoked synaptic potentials of striatal projection neurons of direct and indirect pathways

Orthodromic stimulation has revealed great differences in the subthreshold and suprathreshold synaptic response kinetics of direct vs. indirect striatal projection neurons: dSPNs vs. iSPNs. Global synaptic responses of both neuron classes involve AMPA, NMDA and GABA_A synaptic potentials differentially distributed throughout the somatodendritic membrane. Although both responses may outlast a single initial stimulus for hundreds of milliseconds, iSPNs postsynaptic responses fire briefer action potential trains and exhibit an initial faster repolarization than those from dSPNs. Experimental evidence suggests that this divergence is due to different proportions of Ca_V3 (T) Ca²⁺ channels in dendritic compartments, leading to a differential activation of Ca²⁺-activated K⁺-channels, and therefore, particular contributions of synaptic inputs. In this computational work, we follow previous experimental evidence to find an efficient and minimal configuration of these currents to simulate the subthreshold and suprathreshold synaptic responses that have been reported for these neuron classes, while anatomical constraints remained constant. The Results illustrate intriguing GABAergic influences in the synaptic integration of dSPNs and iSPNs and important functional differences between the basal ganglia pathways that they originate.